Allogeneic hematopoietic cell transplantation following chimeric antigen receptor T-cell (CAR-T) therapy in B-cell acute lymphoblastic leukemia (B-ALL): A systematic review and meta-analysis.

Abstract

e18577 Background: Chimeric antigen receptor T-cell (CAR-T) therapy induces high initial response rates in B-cell acute lymphoblastic leukemia (B-ALL); however, relapse remains frequent. The impact of allogeneic hematopoietic cell transplantation (allo-HCT) following CAR-T therapy on long-term outcomes remains uncertain. We performed a meta-analysis to evaluate survival and relapse outcomes associated with allo-HCT after CAR-T therapy in B-ALL. Methods: Eligible comparative studies evaluating allo-HCT after CAR-T therapy versus no transplant were identified through a systematic search following PRISMA guidelines. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted for overall survival (OS), leukemia-free survival (LFS), and relapse. Pooled estimates were calculated using inverse-variance methods. Fixed-effects models were applied when heterogeneity was minimal (I²<50%); random-effects models were used otherwise. Heterogeneity was assessed using Cochran’s Q and I² statistics. Publication bias was assessed qualitatively using funnel plots. Results: Five retrospective studies encompassing 127 patients were included. Cohorts included pediatric, adolescent/young adult, and adult patients with relapsed/refractory B-ALL (median ages of 11-44 years across studies; male predominance, when reported). Most patients achieved complete remission (CR) with minimal residual disease (MRD) negativity post-CAR-T (MRD-negative pre-HCT in 78–93% of reported cases). Donors were unrelated in 39%, matched siblings in 31%, and haploidentical in 30% of reported cases (n=93 donors); conditioning regimens included cyclophosphamide/fludarabine or TBI-based myeloablative approaches. The median interval from CAR-T infusion to allo-HCT was approximately 3 months (range 2–10 months). Three studies contributed to the OS analysis and five to the LFS analysis. Allo-HCT after CAR-T was associated with improved OS (pooled HR 0.49; 95% CI, 0.33–0.72; p=0.0004; I²=0%). LFS was also improved (HR 0.30; 95% CI: 0.16–0.55; p=0.0001; I²=80.9%). Relapse risk was markedly lower with allo-HCT (HR 0.16; 95% CI: 0.10–0.23; p<0.001; I²=0%; two studies). Transplant-related mortality ranged 3-29% across reports, with notable acute/chronic graft-versus-host disease and infections. Conclusions: Allo-HCT following CAR-T therapy was associated with improved survival in selected patients with B-ALL, driven primarily by reduced relapse risk. These findings support further prospective evaluation of allo-HCT after CAR-T therapy.